Monday, July 23, 2012

Datura, Bacon, and Enhancement of the Brain

Bacon's Rebellion

In 1674, Virginia... the first rebellion in an American colony occurred when planter Nathaniel Bacon issued his “Declaration of the People of Virginia.” He wasn't angry regarding taxes, or freedoms lost, etc... he was angry because the Governor refused to drive Native Americans from their treaty protected lands. It's an interesting event in history in that it contains elements of both racial injustice and tolerance. Bacon's militia attacked and killed men of American Indians tribes who had always been allies of the English, a brutish demonstration of prejudice. His militia though, was composed of whites and blacks alike who fought side by side not only against the natives, but also against a Governor widely despised for his oppression of any religion aside from the Church of England.

According to the 1705 work, “The History and Present State of Virginia, in Four Parts,” a group of soldiers sent to quell the rebellion were served the young leaves of a plant called the “James-Town Weed." The soldiers, subsequent behaviors were found to be quite startling:

One would blow up a Feather in the Air; another wou'd dart Straws at it with much Fury; and another stark naked was sitting up in a Corner, like a Monkey, grinning and making Mows at them; a Fourth would fondly kiss, and paw his Companions, and snear in their Faces, with a Countenance more antick, than any in a Dutch Droll. In this frantick Condition they were confined, lest they should in their Folly destroy themselves; though it was observed, that all their Actions were full of Innocence and good Nature. Indeed, they were not very cleanly; for they would have wallow'd in their own Excrements, if they had not been prevented. A Thousand such simple Tricks they play'd, and after Eleven Days, return'd to themselves again, not remembring any thing that had pass'd.

This plant, Datura stramonium, grows wild wherever it is temperate and its many common names include Jimson Weed, Datura, Thorn-apple, and Locoweed (which can refer to a number of other non-related plants as well such as Milkvetch.) Datura, used both as a recreational drug and as an entheogen, results in a number of deaths each year. The active psychotropic compounds found in Datura includes Atropine and Scopolamine, both of which are anticholinergics. The strength of atropine and scopolamine however are very different. A 1.5mg patch of Scopolamine is used to prevent seasickness, whereas a dose 0.5mg of atropine is used only in the emergency resuscitation of those suffering from severe bradycardia and heart blocks. According to “Poisonous Plants and Animals of Florida and the Caribbean,” the ratio of scopolamine to atropine is 3:1 in young leaves, and then reverses to a 1:3 ratio after the plant has flowered. The consumption of only the very young “James-Town weed” is likely the reason that the men survived to not remember their experience.

Scopolamine and Memory Research

Scopolamine Molecule

Another use of scopolamine beyond the treatment of seasickness is in memory research. Scopolamine has long been known to inhibit the formation of memories and has even been used in Thailand by criminals who were later unable to be recognized by the victim. They simply couldn't remember who the thieves were. A 2004 study, “Patterns of memory failure after scopolamine treatment: Implications for cholinergic hypotheses of dementia” found that as little 0.5mg was effective at impairing acquisition and delayed the speed at which the participants were able to recall words.

Scopolamine is an anticholinergic which means it decreases the effects of the neurotransmitter Acetylcholine through competitive inhibition. For example, the Vagus nerves leading to your heart carry parasympathetic signals. The neurotransmitter it uses is Acetylcholine, which slows the heart rate down. When a person is given scopolamine, it competes against the Acetylcholine for the receptors of the heart. Although it binds to the receptors, it doesn't activate them. With less Acetycholine the heart rate begins to climb. This is great in the case of atropine being used on a person with a very low heart rate, but not so great for a 14-year-old boy eating leaves to get high. Acetylcholine also performs many functions within the central nervous system including modulating plasticity, arousal, and carries out significant roles in the formation of memories. This explains the loss of memory associated with Scopolamine. By competing with the CNS acetylcholine, the subject has a decrease in arousal and difficulty forming new memories.

In memory research, scopolamine is used to simulate memory loss such as occurs in Alzheimer's or dementia. A group of rats are given a dose of scopolamine and provided with a memory task. The control rats inevitably show difficulties. The treatment group is given a substance and if they show less of a decrease in ability at the memory task compared to the control group, the substance is deemed effective at enhancing memory formation. One such substance is Piracetam.

Pharmacological Enhancement of the Brain:

Nootropics

A 1987 study, “Reversal of scopolamine-induced amnesia and alterations in energy metabolism by the nootropic piracetam: implications regarding identification of brain structures involved in consolidation of memory traces” found that administration of Scopolamine significantly reduced the use of glucose by cells in the Hippocampus, a region of the brain closely associated with the formation of memories. Administration of the compound Piracetam was found to completely reverse this Scopolamine-induced Hippocampal depression.

This study was important because the same reduction in glucose used by the Hippocampus has been found in the brains of those suffering from Alzheimer's disease. Many studies have since elucidated the effectiveness of Piracetam in treating Alzheimer's. Piracetam is a prescription drug throughout most of Europe but not currently in use in the United States.

This brings us to the point of this blog: Piracetam has also been shown to be effective in increasing the mental faculties of healthy adults as well. One double-blind placebo controlled study found an increase in the verbal memory abilities of healthy college students (Increase in the power of human memory in normal man through the use of drugs.) Another study, “Piracetam-induced improvement of mental performance” which assessed perceptual motor tasks found that in “a majority of these tasks the subjects did significantly better when on piracetam than on placebo, a finding consistent with ratings completed by two independent observers.”

So there we have it! An augmentation to intelligence that is as simple as taking a pill.

Welcome to the world of nootropics my friend. Piracetam was first synthesized in 1964 by Romanian chemist Corneliu E. Giurgea. He created the word Nootropic from the Greek words Nous and trepein. Nous means mind, and trepein means to bend, so Nootropics are compounds with a mind bending effect. Dr. Mindbender Giurgea strongly believed that the future lies in the enhancement of the mind through nootropic drugs. In his words,

"Man is not going to wait passively for millions of years before evolution offers him a better brain."

Piracetam was the first, but it certainly hasn't been the last. There have now been scores of different compounds identified as enhancing different functions of the brain. I've played with nootropics for years and intend to write further blogs extolling their individual virtues. I choose piracetam because its safety has been demonstrated for nearly 60 years, it's relatively inexpensive, and nearly every person I've ever known who supplements with nootropics started out with it. So let's take a closer look at this drug.

Sources and Pricing

From my experience, Cognitive Nutrition provides fast shipping and has pricing at the lower end of the scale. You can find products for less, but they often feel like fly-by-night operations. I would personally wonder if I was being sold expensive baking soda. Cognitive Nutrition has been around for quite some time and has a good reputation amongst those who experiment with Nootropics (There are whole online communities centered around nootropics by the way.) Cognitive Nutrition is affordable with reliable service. (Added note: I was informed by Cognitive Nutrition that they have always been cGMP compliant, and that they provide certificates of analysis for any item they stock per request. Cognitive Nutrition's product are also sold through many other retailers, as well as to Doctors, Pharmacies and Clinics.)

Relentless Improvement seems to me an attempt at being the flagship of Nootropic suppliers. They certainly aren't the cheapest. In fact, products from RI are often twice the price of other suppliers, although in the case of Piracetam they are pretty competitive. They have one major thing going for them though and that is independent quality testing. All of these guys are essentially getting their raw compounds from the same place: China. Relentless Improvement has an independent company perform an analysis on all of its Piracetam and even provides copies of the certificate. They also use all Veg caps as well for the vegetarians out there. Relentless Improvement provides a highly reliable product.

I have to say, I'm very fond of Cerebral Health. Let's start with the “criticism.” In 2011, CH failed an FDA Good Manufacturing Practice Inspection. I tell you this because if you look up reviews on CH, it will be the first thing you find. Reading the actual violations though, you find these violations to be things like a failure to have a written master manufacturing record, and failure to have a written procedure to review complaints about products from customers. I've never seen any evidence that the company provides anything but the highest quality product. Something to take note of though is that Cerebral Health provides Piracetam in the form of bulk powder, not capsules. So you have the option of packing 'em yourself or mixing it in water. It's not the tastiest treat around, but it's not too bad. The major advantage? They have fantastic prices.

(Added note. After contacting Cerebral Health, I was given an update that a further FDA Inspection was done which found all violations fixed and they are now in compliance. Good company!)

Price: 10.00 for 100 Grams Bulk Powder

This breaks down to 10 cents per gram! Of course keep in mind that you'll need to measure out each dose and it's far less convenient than the capsules are.

Dosage

The proper dosage for Piracetam is widely debated. Many of the memory experiments using rats had doses of around 100mg/kg. In a 200 lb male this would equate to something around 9 grams of the stuff. This would be a little over 12 of the widely available 800mg capsules. This isn't unheard of or anything but I think most would consider it to be overkill. 1600Mg of piracetam 2-3 times a day is a pretty run of the mill dosing schedule. In a 200 lb male, this dose is around 18mg/kg. Far, far lower than the experimental doses.

I'll tell you my personal and arbitrary opinion and feelings regarding a good starting dose. I would start with 3.2 grams of Piracetam and redose myself every 4-6 hours while awake. Notice I didn't even take into account weight? So you can't take this advice too seriously. It's just based on my personal experiences. Most people will be able to discern its effect beyond that of placebo at 3.2 grams. Then one can experiment with increasing and decreasing the dose in order to find what works best for them. Many people state that they get better results with lower doses (also subjective) so don't assume that more is better than less. In fact, at higher doses some people complain that they get a “brain fog” and can no longer think as clearly as at baseline.

Mechanism of Action

I don't know if I should call this unknown or too diverse to mention. The mechanism of Piracetam has been studied in great detail. Some studies seem to suggest that Piracetam is an allosteric regulator, which means it binds to a different site than where the ligand normally binds and changes the receptors affinity for its ligand. So perhaps Piracetam works by changing how well neurotransmitters bind to cells. Other studies have shown Piracetam being active at voltage gated Ion channels such as calcium channels. There is one idea that has been completely ruled out. Piracetam does not function as an agonist. It does not directly mimic the neurotransmitter Acetylcholine, and in fact the molecule looks a whole lot more like GABA than it does Ach.

This is important to note because of a strange effect I mentioned above. This effect is often referred to as a “brain fog.” Which leads us into the side effects of Piracetam.

Side Effects and The Use of Choline

In rare cases people experience insomnia, irritability, headache, agitation, and nervousness. This compound has been used since the 1960s though, and I have yet to dig up any substantiated reports of someone suffering anything worse than a headache and some anxiety that goes away once one stops taking it. It's about as safe as something can be. Some people complain that Piracetam in higher doses instead of aiding cognition actually fogs their brain. Don't fret though! The solution is to co-administer the piracetam with a choline source such as lecithin, choline bitartrate , or Alpha GPC. A combination of Piracetam and a choline source is usually the first “stack” that people play with as they become introduced to the world of Nootropics. I will explore the pros and cons of the variety of choline sources in a later blog.

The use of this combination, a choline source and piracetam, have no supporting studies I know of to suggest any synergistic increase in cognitive ability, or a decrease in the “brain fog” side effects of Piracetam. Many use the reasoning that Piracetam increases the use of Acetylcholine and somehow causes a person to “run out.” The reason I bring this combination up though, is because over the last 30-40 years of use, people have time and time again subjectively reported that piracetam with a choline source is both more effective and preventative of brain fog. I myself have experienced this so-called “brain fog” when I wasn't using a choline source, but never while I was.

Your personal experience with nootropics honestly is the only one that matters though. I have seen many, many people who state that Piracetam does absolutely nothing for them. This hasn't been my experience, but it may be yours. And no Nootropic at this point will do the things from the movie Limitless. God, I wish they could, but I've taken most of the widely available nootropics out there and quite a few of the much harder to get substances, and I can tell you that effects are usually pretty subtle. Don't be too disappointed if the solution to cold fusion doesn't come to you in a dream.

Where do I go from here?

I fully suggest anyone who is interested in Pharmocological Augmentation of the Brain to do two things.

Explore the actual research being done on these subjects, and no I don't mean wikipedia. The use of a good science search engine such as Scirus can provide your with a lot of good results. Even better is to get access to a database such as EBSCOhost. Paying for personal access is a rip, but one can usually find a student login from a college by scouring the internet (Of course you'd legally have to be a student at said college and I would advise anyone to break a law. Instead of depending on someone such as me to interpret the research, go see what is known for yourself.

Join a few online communities to see what experiences others are having with these substances. I'm fond of Brainmeta and Longecity, which both have pretty solid groups of people using Nootropics. In fact, the suppliers I listed above are often on these forums answering questions about their products.

To conclude, I think it goes without saying that a substance with a 40 year record of being completely safe, that can increase one's mental faculties is an augmentation worth considering. Piracetam is not the most powerful Nootropic available by a long shot, but it is the first Nootropic identified and a great place to start. If for some reason you are one of those who sees no affect, no cognitive benefit from Piracetam, keep in mind that you have been granted an ability beyond that of a normal human. If you and your buddies ever get together to oppress the natives and fight the Church of England,

you can be confident that you will be able to remember sitting naked in the corner and wallowing in your own excrement after eating that special, delicious salad. Oh hey, and if you got anything out of this article please consider clicking on the ad below.